Use of itaconate and its derivatives/analogues to induce hair growth

Abstract

Methods for the use of prodrugs of itaconic acid and 1- and 4-methyl itaconic acid for inducing hair growth and treating an inflammatory, or immune activation (adaptive or innate), skin condition or other condition associated with hair loss are disclosed.

What is claimed is: 
     
         1 . A method for inducing hair growth or treating a hair loss condition in a subject, the method comprising administering to the subject a therapeutically effective amount of a compound of formula (I): 
       
         
           
           
               
               
           
         
         wherein:
 R 1  is 
 
       
       
         
           
           
               
               
           
         
       
       wherein n is an integer selected from 1, 2, 3, and 4; R 4  is C 1 -C 6  straight-chain or branched unsubstituted or substituted alkyl or —OR 5 , wherein R 5  is C 1 -C 6  straight-chain or branched unsubstituted or substituted alkyl; and
  R 2  is —OR 3 , wherein R 3  is C 1 -C 6  straight-chain or branched unsubstituted or substituted alkyl. 
 
     
     
         2 . The method of  claim 1 , wherein
 R 1  is   
       
         
           
           
               
               
           
         
       
       wherein n is an integer selected from 1 and 2; R 4  is C 1 -C 6  straight-chain or branched unsubstituted or substituted alkyl or —OR 5 , wherein R 5  is C 1 -C 6  straight-chain or branched unsubstituted or substituted alkyl; and
 R 2  is —OR 3 , wherein R 3  is C 1 -C 6  straight-chain or branched unsubstituted or substituted alkyl. 
 
     
     
         3 . The method of  claim 2 , wherein 
       
         
           
           
               
               
           
         
         R 1  is n is an integer selected from 1 and 2; R 4  is —OR 5 , wherein R 5  is C 1 -C 6  straight-chain or branched unsubstituted or substituted alkyl; and 
         R 2  is —OR 3 , wherein R 3  is C 1 -C 6  straight-chain or branched unsubstituted or substituted alkyl. 
       
     
     
         4 . The method of  claim 2 , wherein
 R 1  is   
       
         
           
           
               
               
           
         
       
       and R 2  is —OCH 3 . 
     
     
         5 . The method of  claim 1 , wherein the compound of formula (I) is selected from: 
       
         
           
           
               
               
           
         
       
       and pharmaceutically acceptable salts thereof. 
     
     
         6 . A method for inducing hair growth or treating a hair loss condition in a subject, the method comprising administering to the subject a therapeutically effective amount of a compound having the structure: 
       
         
           
           
               
               
           
         
       
     
     
         7 . A method for inducing hair growth or treating a hair loss condition in a subject, the method comprising administering to the subject a therapeutically effective amount of a compound having the structure: 
       
         
           
           
               
               
           
         
       
     
     
         8 . A method for inducing hair growth or treating a hair loss condition in a subject, the method comprising administering to the subject a therapeutically effective amount of a compound having the structure: 
       
         
           
           
               
               
           
         
       
     
     
         9 . The method of  claim 1 , further comprising a pharmaceutical composition comprising a compound of formula (I) and a pharmaceutically acceptable excipient. 
     
     
         10 . The method of  claim 1 , wherein the hair loss condition is selected from alopecia areata, androgenic alopecia, anagen effluvium, self-induced hair loss, telogen effluvium, and scarring alopecia. 
     
     
         11 . The method of  claim 10 , wherein the alopecia areata comprises patchy alopecia areata. 
     
     
         12 . The method of  claim 10 , wherein the alopecia areata comprises alopecia totalis. 
     
     
         13 . The method of  claim 10 , wherein the alopecia areata comprises alopecia universalis. 
     
     
         14 . The method of  claim 1 , wherein the method for inducing hair growth induces a transition from a telogen phase to an anagen phase of a hair growth cycle. 
     
     
         15 . The method of  claim 14 , further comprising increasing a number of hair follicles present in the subject in the anagen phase. 
     
     
         16 . The method of  claim 15 , wherein the subject has a decreased number of hair follicles in the anagen phase relative to a control subject prior to administering a therapeutically effective amount of a compound of formula (I).